HCV Drug Combo Has Near-Perfect Response Rate

BOSTON -- A combination of three investigational drugs for hepatitis C (HCV) led to cures in more than 99% of patients with the most common viral genotype, a researcher said here.

The combination was equally efficacious with or without ribavirin, one of the standard drugs used to treat the virus, according to K. Rajender Reddy, MD, of the University of Pennsylvania in Philadelphia.

In the PEARL-III trial, Reddy and colleagues were testing three direct-acting agents:

ABT-450/r, an HCV protease inhibitor boosted with ritonavir (Norvir)

ABT-267, an NS5A inhibitor

ABT-333, a non-nucleoside NS5B inhibitor

The combination has been dubbed "three-D" even though it actually includes four drugs.

The first two drugs were co-formulated in a single pill and the combination was tested with or without ribavirin, a general anti-viral used mainly to treat HCV, in 419 patients with genotype 1b infection.

The primary endpoint was the noninferiority of sustained virological response 12 weeks after the end of treatment (SVR12) with the three-D regimen compared with an historical marker in a similar population treated with telaprevir (Incivek) and pegylated interferon-alfa plus ribavirin.

A key secondary endpoint was noninferiority of the three-D regimen with ribavirin to the combination without the drug.

In both arms of the study, at least 99% of patients achieved an SVR12 (99.5% with ribavirin and 99% without). That was substantially noninferior to the 73% seen with the telaprevir-based regimen, Reddy noted, and in fact beat the threshold that would demonstrate superiority.

The addition of ribavirin to the three-D regimen did not provide any extra clinical benefit, he said.

Only three patients failed to achieve SVR12. One person in the ribavirin arm had a virologic failure while on treatment owing to the emergence of a resistance mutation, and two in the other arm were lost to follow-up.

There was no difference in response rates by race, sex, or the presence of a genetic variant that is known to predict a poor response to peginterferon.

The major adverse events were headache, fatigue, pruritus, nausea, and asthenia, with rates of pruritus and nausea significantly greater in the ribavirin arm (at P=0.02 and P=0.01, respectively).

The results are about as good as they can be, with or without ribavirin, commented Jean-Michel Pawlotsky, MD, PhD, of Henri Mondor University Hospital in Créteil, France, who moderated a press conference at which some details were presented.

"It's difficult to do better," he told MedPage Today.

On the other hand, he noted, genotype 1b is an "easy-to-treat genotype" and results informally released suggest ritonavir might be needed, for instance, in patients with HCV genotype 1a in order to get similar outcomes.

Formal presentation of data for other genotypes is expected at a liver conference in Europe next month, Pawlotsky said.

But so far the data suggest the combination is "excellent for everything," Pawlotsky said, possibly because the use of ritonavir to boost the protease inhibitor ABT-450 helps to overcome resistant strains of HCV.

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